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CLINICAL RESEARCH: HEART FAILURE AND CARDIAC TRANSPLANT

Peritransplant Ischemic Injury Is Associated With Up-Regulation of Stromal Cell-Derived Factor-1

Mohamad H. Yamani, MD^_*,_*, Norman B. Ratliff, MD, Daniel J. Cook, PhD, E. Murat Tuzcu, MD^_*, Yang Yu, MS^_*, Robert Hobbs, MD^_*, Gustavo Rincon, MD^_*, Corinne Bott-Silverman, MD^_*, James B. Young, MD^_*, Nicholas Smedira, MD and Randall C. Starling, MD, MPH^_*

^_* Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio.
Department of Anatomic Pathology, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio.
Department of Cardiothoracic Surgery, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio.
Department of Allogen Laboratory, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio.

Manuscript received February 21, 2005; revised manuscript received April 24, 2005, accepted April 25, 2005.

^_* Reprint requests and correspondence: Dr. Mohamad H. Yamani, Cardiovascular Medicine, F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. (Email: yamanim{at}ccf.org).

OBJECTIVES: We evaluated chimerism and stromal cell-derived factor-1 (SDF-1) expression in response to peritransplant ischemic injury following human heart transplantation.

BACKGROUND: Myocardial ischemia has been shown to trigger mobilization of stem cells to the heart in animal experiments.

METHODS: Between January 1998 and April 2002, a total of 114 male recipients received hearts from female donors. Of these 114 recipients, 26 had evidence of ischemic injury on their initial heart biopsies (ischemia group). These were compared to the remaining 88 patients (control group). Heart biopsy specimens obtained initially at one week and at one year after transplant were evaluated from 20 matched patients of each group for the presence of Y chromosome-containing nuclei. The SDF-1 messenger ribonucleic acid (mRNA) and protein expression were also evaluated on initial heart biopsy specimens.

RESULTS: At one week, Y chromosome-containing nuclei were significantly increased in the ischemia group (0.68% vs. 0.04%; p < 0.0001) compared to the control group. These were positive for the stem cell factor receptor c-kit. A significant 3.3-fold increased mRNA expression (p = 0.001) and 2.8-fold increased protein expression (p = 0.01) of SDF-1 was noted in the ischemia group. At one year, Y chromosome was detected in 0.29% of cardiomyocyte nuclei in the ischemia group but none in the control group. The ischemia group had poorer survival and increased vasculopathy.

CONCLUSIONS: This is the first report to describe chimerism and up-regulation of SDF-1 in human heart transplantation in response to ischemic injury.

Abbreviations and Acronyms   FISH = fluorescent in situ hybridization   mRNA = messenger ribonucleic acid   RT-PCR = reverse transcription-polymerase chain reaction   SDF-1 = stromal cell-derived factor-1

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